Insulin deficiency causes growth arrest in untreated juvenile diabetics. Experimental and clinical observations suggest that insulin is required for the generation of somatomedin in response to growth hormone. The liver has been shown to be a site of somatomedin generation. The generation of somatomedins by growth hormone is not well defined at present. Establishment of a model in hepatic cell tissue culture would facilitate study of this phenomenon. This proposal is to identify a tissue culture system of rat hepatic origin which generates somatomedin bioactivity when incubated with growth hormone. Such a system would allow clarification of the mechanism of somatomedin generation. The influence of insulin in this system will be investigated with the goal of clarifying the pathophysiology of growth defects in diabetes.